This proposal describes a series of acute and chronic studies to be performed in subjects with idiopathic hypercalciuria to test three alternative hypotheses for the pathogenesis of this disorder. The basis for these hypotheses are the observations that increased intestinal calcium absorption, reduced renal tubule calcium reabsorption and hypophosphatemia are found in this disorder. The three models are based on the primacy of each of the above observations and serum parathyroid hormone levels. Each model predicts a specific pattern of response of serum immunoreactive parathyroid hormone, 1,23-dihydroxy vitamin D, intestinal calcium absorption and renal tubule calcium reabsorption under given conditions. We propose to measure selected parameters in response to parathyroid hormone infusion, EDTA infusion, chronic dietary calcium restriction and chronic thiazide therapy. Either idiopathic hypercalciuria is heterogenous, based upon more than one pathogenetic scheme, or we must assume that a unitary hypothesis can be found that encompasses all patients with the syndrome and is consistent with the results of these proposed studies.